Clinical Topic A-Z Clinical Speciality

Chilblains

Chilblains
D002647Chilblains
Skin and nail
2013-08-01Last revised in August 2013

Chilblains - Summary

Chilblains (also known as perniosis or pernio) are localized inflammatory skin lesions on exposed extremities of the body, precipitated by cold.

Chilblains can be classified as:

Acute — developing within 12–24 hours after exposure to cold and lasting 1–2 weeks, provided that further cold exposure is avoided.

Chronic — occurring with repeated exposure to cold, resulting in persistent lesions which can lead to subsequent scarring and atrophy.

Chilblains can be idiopathic or secondary to other diseases (such as systemic lupus erythematosus).

Risk factors for chilblains include:

A history of Raynaud's phenomenon.

Low body mass index.

Systematic lupus erythematosus.

Dysproteinaemias and myelodysplastic disease.

Complications include:

Skin excoriation from scratching.

Secondary infection from blistered or scratched chilblains.

Ulceration.

Permanent discolouration.

Scarring.

Chilblains are diagnosed on clinical grounds and should be suspected when a person has one or more intensely itchy, painful, swollen skin lesions that appear within 12–24 hours of exposure to cold.

The lesions appear as single or multiple (usually symmetric) red patches, papules, or plaques on a cool, oedematous base.

They occur most commonly on the toes and fingers, but also on the face (nose, cheeks, and the ear lobes) and legs (heels, shins, thighs, and hips).

The colour can change from red to purple (or marked darkening in people with dark skin), and swelling can progress to painful, deep purple indurations. In severe cases, it can lead to blistering or ulceration.

Arterial circulation is normal.

People presenting with an acute or recurrent episode of chilblains should be reassured that the condition is self limiting, caused by exposure to cold, and will resolve if further exposure to cold is avoided.

The following should be advised:

Dressing warmly to protect the fingers, hands, head, ears, and feet from cold.

Keeping dry to reduce heat loss.

Avoiding scratching, rubbing, or applying direct heat.

Smoking cessation, if relevant.

Over-the-counter topical preparations are not recommended.

Drug treatment should not be routinely prescribed, but may be considered for severe chronic chilblains and recurrent episodes of severe chilblains that do not respond to appropriate self-care measures.

If needed, modified-release nifedipine 20 mg daily is an option. If not tolerated, a lower dose may be considered using immediate-release nifedipine 5 mg capsules (less preferred). The dose can be titrated up to a maximum of 60 mg daily.

Treatment should be discontinued if the response is inadequate at the maximal tolerated dose.

Treatment should continue until the lesions have healed, or for the rest of the cold season if prophylaxis is indicated.

Have I got the right topic?

1months3060monthsBoth

This CKS topic covers the management of chilblains.

There is a separate CKS topic on Raynaud's phenomenon.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

CKS gratefully acknowledges the contribution of the British Association of Dermatologists in the development of this topic.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in August 2013

August 2013 — reviewed. A literature search was conducted in July 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to recommendations have been made.

Previous changes

July to November 2009 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 July 2013.

HTAs (Health Technology Assessments)

No new HTAs since 1 July 2013.

Economic appraisals

No new economic appraisals relevant to England since 1 July 2013.

Systematic reviews and meta-analyses

No new systematic review or meta-analysis since 1 July 2013.

Primary evidence

No new randomized controlled trials published in the major journals since 1 July 2013.

New policies

No new national policies or guidelines since 1 July 2013.

New safety alerts

No new safety alerts since 1 July 2013.

Changes in product availability

No changes in product availability since 1 July 2013.

Goals and outcome measures

Goals

To accurately diagnose chilblains

To advise self-care measures for the management and prevention of chilblains

To prescribe drugs appropriately for the treatment and prevention of severe chilblains

Background information

Definition

What is it?

Chilblains (also known as perniosis or pernio) are localized inflammatory skin lesions on exposed extremities of the body. They are precipitated by cold (see Causes) [Goette, 1990; Almahameed and Pinto, 2008].

Chilblains can be classified as [Leger and Boccalon, 1997; Simon et al, 2005]:

Acute — developing within 12–24 hours after exposure to cold and lasting 1–2 weeks, provided that further cold exposure is avoided.

Chronic — occurring with repeated exposure to cold, resulting in persistent lesions which can lead to subsequent scarring and atrophy.

Causes

What causes it?

Chilblains can be idiopathic or secondary to other diseases (such as systemic lupus erythematosus) [Parlette and Parlette, 2000].

Chilblains are thought to be caused by intermittent or prolonged cold-induced vasoconstriction, with subsequent hypoxemia and inflammation of the vessel wall [Goette, 1990; Giusti and Tunnessen, 1997; Prakash and Weisman, 2009].

Although coldness is a recognized trigger of chilblains, there is controversy about whether dry cold or damp cold is more likely to cause them [Simon et al, 2005].

Prevalence

How common is it?

Although chilblains are regarded as relatively common in European countries with damp, non-freezing, cold climates, CKS identified no reliable data on the prevalence of chilblains in the UK.

Chilblains can occur at all ages but are more common in children and elderly people.

Chilblains are more common in women than men.

Chilblains affect all races.

[Goette, 1990; Leger and Boccalon, 1997; Parlette and Parlette, 2000; Jordaan, 2007; Almahameed and Pinto, 2008; Prakash and Weisman, 2009]

Risk factors

What are the risk factors?

Risk factors for chilblains include [Goette, 1990; Almahameed and Pinto, 2008; Prakash and Weisman, 2009; Kennedy et al, 2010]:

A history of Raynaud's phenomenon.

Low body mass index (including people with anorexia nervosa).

Systematic lupus erythematosus.

Dysproteinaemias and myelodysplastic disease.

Although not documented to cause chilblains, drugs such as beta-blockers (for example, propranolol) are known to cause cold extremities as well as exacerbation of Raynaud's phenomenon [Aronson, 2006]. Consequently, these drugs may exacerbate chilblains or increase the risk of recurrence in people with chilblains.

Complications

What are the complications?

Complications of chilblains are:

Skin excoriation from scratching.

Secondary infection from blistered or scratched chilblains.

Ulceration.

Permanent discolouration.

Scarring.

Complications are more likely in the presence of arterial or systemic disease.

Complications can be exacerbated by applying excessive heat directly to the skin or repeatedly rubbing or scratching the lesion.

[Almahameed and Pinto, 2008]

Prognosis

What is the prognosis?

Idiopathic chilblains are self limiting.

If further exposure to cold is avoided, chilblains generally resolve after 1–3 weeks, depending on their severity.

The condition may recur during cold seasons. However, it disappears in spring or early summer.

[Goette, 1990; Leger and Boccalon, 1997; Parlette and Parlette, 2000; Simon et al, 2005; Jordaan, 2007; Almahameed and Pinto, 2008]

Diagnosis

Diagnosis of chilblains

Diagnosis

How do I know my patient has it?

Chilblains are diagnosed on clinical grounds.

Suspect chilblains in people with one or more intensely itchy, painful, swollen skin lesions that appear within 12–24 hours of exposure to cold.

The lesions appear as single or multiple (usually symmetric) red patches, papules, or plaques on a cool, oedematous base. They are usually accompanied by intense itching, burning, or pain.

They are found on exposed extremities, most commonly the toes and fingers. The face (nose, cheeks, and the ear lobes) and legs (heels, shins, thighs, and hips) can also be affected.

The colour can change from red to purple (or marked darkening in people with dark skin), and swelling can progress to painful, deep purple indurations. In severe cases, it can lead to blistering or ulceration.

Arterial circulation is normal on physical examination.

Investigations for chilblains are generally not indicated but should be considered if the history or examination raise the possibility of a systemic cause (such as systemic lupus erythematosus) or if the person's history does not indicate excessive cold exposure (for example consider a full blood count to exclude haematological disorders). Consider seeking specialist advice if in doubt.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion [Jacob et al, 1986; Goette, 1990; Giusti and Tunnessen, 1997; Leger and Boccalon, 1997; Parlette and Parlette, 2000; Simon et al, 2005; Almahameed and Pinto, 2008; Prakash and Weisman, 2009; Kennedy et al, 2010].

Investigations for chilblains

Laboratory investigations are of little value, as the findings are generally normal [Leger and Boccalon, 1997].

Skin biopsy is not recommended by experts [Leger and Boccalon, 1997; Parlette and Parlette, 2000; Almahameed and Pinto, 2008]. This is because a definitive histopathologic pattern for chilblains cannot be established, owing to the extensive heterogeneity between sampled lesions, presence of secondary complications (such as infection), and histologic similarities with other disease states (such as peripheral arterial disease) [Almahameed and Pinto, 2008].

Where the diagnosis of chilblains is uncertain (for example, if the lesions are persistent, atypical or presenting with other manifestations), some experts recommend further diagnostic studies such as skin biopsy and laboratory tests (for example, full blood count, rheumatoid factor, antinuclear antibody titre, cryoglobulin, cold agglutinin, and cryofibrinogen) to exclude conditions such as connective tissue disease, cryopathy, or haematological disorders [Almahameed and Pinto, 2008]. Consequently, CKS recommends seeking specialist advice if there is uncertainty regarding diagnosis.

Differential diagnosis

What else might it be?

The differential diagnosis of chilblains is broad and depends on the stage of the disease at presentation as well as the appearance and location of the lesions.

The differential diagnosis of chilblains includes:

Raynaud's phenomenon

See the CKS topic on Raynaud's phenomenon.

Chilblain lupus erythematosus

This is secondary to systemic lupus erythematosus.

The condition can mimic idiopathic chilblains, with skin lesions similar to those seen in people with chilblains.

Acrocyanosis

The fingers, toes, and other extremities have a bluish discolouration, which blanches with pressure and intensifies with cold or strong emotion.

There is no pain and no atrophic changes.

Acrocyanosis is more commonly seen in thin, sedentary women.

Cold urticaria

The lesions are not restricted to the peripheral areas of the body.

The lesions can be reproduced by applying an ice cube to the skin.

Conditions associated with blue toes (due to arterial insufficiency or drug-induced)

Atheromatous embolization.

Thrombotic embolization.

Peripheral arterial disease.

Blue toe syndrome — adverse effect associated with warfarin treatment (rare).

Conditions associated with erythematous, nodular, and ulcerative lesions

Erythema nodosum

May be associated with fever, arthralgias, and malaise.

May be primary or secondary to an underlying disease.

Lesions are painful but do not ulcerate.

Cold panniculitis

Lesions may be reproduced by applying an ice cube to the skin.

Histology reveals fat necrosis.

Erythema multiforme

This is an immune-mediated disease.

It is characterized by target lesions, which typically are less than 3 cm in diameter, are round in shape, and have a well-defined outer ring of erythema, a central area of dusky erythema, and a paler oedematous zone in between.

Lesions are usually found on hands and feet but can also appear on oral, conjunctival, and genital mucosae.

Sarcoidosis

Skin lesions of sarcoidosis are generally in the form of nodules or plaques varying in colour from yellow to purple. Scarring is uncommon.

The large nodular type usually involves the face, hands, and trunk, whereas the small nodular type predominantly affects the extensor aspects of the limbs.

Lupus pernio is a relatively common skin manifestation of sarcoidosis and can appear as dusky-red infiltrated plaques (on the nose or occasionally on the fingers, toes, cheeks or ears).

Livedo reticularis

Lesions appear as mottled, cyanotic discolouration of the skin with a characteristic network pattern. It can be widespread or localized.

Causes can be physiological (cold-induced) or pathological (for example, due to connective tissue disease).

Erythema ab igne

Appears as a network of pigmented erythema and commonly affects the legs of women.

It is caused by heat-induced damage.

Telangiectasia

Telangiectases are chronically dilated capillaries or small venules.

They appear as small, dull red, linear, stellate or punctate markings.

Causes include skin atrophy, excess oestrogen (for example, during pregnancy) and connective tissue disease.

Nodular vasculitis — rare

Generally affects women 30–40 years of age.

Develops as recurrent, painful, nodular lesions of the calves which do not generally ulcerate.

There is no relationship to cold exposure.

There is no associated tuberculosis infection.

Erythema induratum (Bazin's disease) — rare

A cutaneous reaction to tuberculosis.

Lesions typically present as nodular, ulcerating lesions on the calves of women.

A tuberculin skin test is usually positive.

Basis for recommendation

Basis for recommendation

This information is based on expert opinion in review articles [Leger and Boccalon, 1997; Almahameed and Pinto, 2008; Hirschmann and Raugi, 2009], Rook's Textbook of Dermatology [Gawkrodger, 2010; Kennedy et al, 2010; Mortimer et al, 2010], and case studies [Jacob et al, 1986; Goette, 1990; Parlette and Parlette, 2000; Viguier et al, 2001; Yang et al, 2009].

Management

Management

Scenario: Management : covers the management of people with chilblains.

Scenario: Management

Scenario: Management of chilblains

1months3060monthsBoth

Overview

Overview of management

For people presenting with an acute or recurrent episode of chilblains:

Reassure that the condition is self limiting and can be prevented.

Offer self-care advice:

On managing the current episode.

To prevent recurrent episodes.

Do not routinely offer drug treatment.

If chilblains are severe, offer nifedipine for treatment and prophylaxis.

Advice

What advice should I offer to someone with chilblains?

Explain that chilblains are caused by exposure to cold and can be prevented.

Although they are uncomfortable, chilblains do not cause permanent damage and will heal on their own if further exposure to cold is avoided.

Chilblains are likely to recur in cold weather; this can be minimized with self-care measures.

Recommend the following measures to minimize exposure to the cold:

Protect the fingers and hands by wearing gloves.

Protect the head and ears by wearing a hat and scarf.

Wear appropriate socks and shoes to insulate the feet from the cold.

Wear adequate clothing to keep the body warm. Clothing should be loose and in layers to trap body heat.

Keep dry to reduce heat loss.

Advise the following to reduce the risk of complications:

Do not scratch or rub chilblains.

Do not directly overheat chilblains (for example using hot water).

Inform the person that no evidence supports the use of over-the-counter topical preparations for chilblains, and they are not recommended (see Treatments not recommended).

These products might be considered by patients as they are widely available to buy over-the-counter (for example, Balmosa®, Deep Heat®, and Mentholatum Vapour Rub®).

These products contain ingredients (such as menthol, camphor, methyl salicylate, capsicum, methyl nicotinate, benzyl alcohol, and eucalyptus oil) that produce a localized vasodilatory, warming, or rubefacient effect.

Encourage smoking cessation.

See the CKS topic on Smoking cessation.

Basis for recommendation

Basis for recommendation

Self-care measures to minimize exposure to cold

These recommendations are based on published expert opinion [Jacob et al, 1986; Leger and Boccalon, 1997; Parlette and Parlette, 2000; Simon et al, 2005; Bielan, 2006; Jordaan, 2007; Almahameed and Pinto, 2008; Prakash and Weisman, 2009].

Although evidence is lacking, these self-care measures are recommended by experts given that chilblains are precipitated and exacerbated by exposure to cold.

Self-care measures are regarded as the key treatment for the management and prevention of chilblains [Leger and Boccalon, 1997; Simon et al, 2005; Almahameed and Pinto, 2008].

Smoking cessation

CKS found no evidence to determine whether smoking is a risk factor for chilblains or whether smoking cessation can alleviate or reduce chilblains.

However, some experts recommend smoking cessation because nicotine is thought to amplify the skin's vasospastic response to cold [Parlette and Parlette, 2000; Almahameed and Pinto, 2008].

When to prescribe

When should I consider prescribing drug treatment for chilblains?

Drug treatment should not be routinely prescribed for the treatment and prevention of chilblains.

If it is prescribed, drug treatment should only be used in addition to self-care measures.

In adults, only consider prescribing drug treatment:

To treat a severe episode of chronic chilblains.

To prevent recurrent episodes of severe chilblains despite appropriate self-care measures.

Seek specialist advice before prescribing drug treatment for:

Children younger than 18 years of age.

Women who are pregnant or breastfeeding.

Adults for whom nifedipine is not suitable or is not tolerated.

Basis for recommendation

Basis for recommendation

Drug treatment is not generally recommended

Routine drug treatment and prophylaxis for chilblains is not recommended by CKS because:

The condition is self-limiting and generally resolves within 1–2 weeks with appropriate self-care measures. These measures are also helpful in preventing recurrence.

The evidence for drug treatment is poor and does not support its routine use in people with chilblains. For further information, see Drug treatment and Treatments not recommended.

Criteria for prescribing drug treatment

The recommendation to offer drug treatment in addition to self-care measures is in line with expert opinion [Leger and Boccalon, 1997; Simon et al, 2005; Almahameed and Pinto, 2008].

Drug treatment for mild-to-moderate chilblains is not recommended because CKS found no evidence or expert opinion to support this.

The recommendation to consider drug treatment for a severe episode of chronic chilblains and to prevent severe chilblains reflects the disease severity of participants in nifedipine trials as well as expert opinion [Giusti and Tunnessen, 1997; Parlette and Parlette, 2000].

Children, and women who are pregnant or breastfeeding

CKS recommends seeking specialist advice for these groups because:

The condition is generally mild and self limiting and responds to self-care measures.

There is no evidence to support drug treatment in these groups.

Although nifedipine can be considered for adults with severe chilblains (off-label indication — see Drug treatment), it is not licensed for use in children for any indication and is not suitable for women who are pregnant (contraindicated) or breastfeeding (safety data are lacking).

People for whom nifedipine treatment is unsuitable or not tolerated

CKS recommends seeking specialist advice for alternative treatment because, apart from nifedipine, the evidence for other treatments is lacking (see Treatments not recommended).

Amlodipine (2.5 mg to 5 mg daily) has been recommended by some experts as an alternative for people who cannot tolerate nifedipine [Jordaan, 2007; Almahameed and Pinto, 2008]. However, CKS found no evidence to support its use for chilblains or to indicate that it is better tolerated than nifedipine.

Drug treatment

What drug treatment should I prescribe for adults with chilblains?

Drug treatment should not be routinely prescribed for chilblains.

If drugs are indicated for the treatment or prophylaxis of severe chilblains:

Consider prescribing nifedipine (off-label indication) in addition to self-care measures.

Other drug treatments are not recommended; see Treatments not recommended.

Initiate therapy with modified-release nifedipine 20 mg daily (preferably with a once-daily formulation).

If this is not tolerated, consider initiating treatment at a lower dose using immediate-release nifedipine 5 mg capsules (less preferred) — for example, 5 mg three times a day.

For more information, see Prescribing information.

Titrate the nifedipine dose upward according to response and tolerability (for example, increase the dose by 10 mg every 1–2 weeks), up to a maximum dose of 60 mg daily.

Monitor the person's blood pressure, as nifedipine may be associated with hypotension.

Discontinue treatment if the response is inadequate after titrating to the maximal tolerated dose.

Continue treatment until the lesions have healed, or for the rest of the cold season if prophylaxis is indicated.

Basis for recommendation

Basis for recommendation

Nifedipine for the treatment and prophylaxis of severe chilblains

Because of its vasodilatory effect, nifedipine is thought to reduce the symptoms and recurrence of chilblains by increasing blood flow to the extremities.

However, the evidence to support the use of nifedipine for the treatment and prophylaxis of chilblains is poor.

Of the four small studies identified (10–36 participants), only one trial had a double-blinded, placebo-controlled design, but it involved only 10 participants.

Consequently, the recommendation to offer nifedipine is based primarily on expert opinion [Leger and Boccalon, 1997; Parlette and Parlette, 2000; Almahameed and Pinto, 2008].

Nifedipine dosage and titration

The recommended nifedipine dosages (off-label use) reflect those used in nifedipine studies on the treatment and prevention of chilblains as well as published expert opinion and case reports [Leger and Boccalon, 1997; Parlette and Parlette, 2000; Jordaan, 2007; Almahameed and Pinto, 2008].

All the nifedipine studies aimed for a daily dose of 60 mg daily. This is based on a small pilot study (10 participants) where the dose was titrated upward from 5 mg daily to the effective or maximal tolerated dose. The most commonly used dose (the modal dose) was 60 mg daily.

Although one small study (34 participants) suggested that a nifedipine dosage of 60 mg daily may be more effective than lower doses, this result should be interpreted with caution because:

Given the small number of people in each treatment group (3–14 participants) and the lack of a placebo group, the benefit of nifedipine dosage on lesion clearance could not be assessed.

More than half of the participants who completed this study could tolerate a nifedipine dose of only 10–40 mg daily.

Consequently, CKS recommends a titration approach when initiating nifedipine treatment, increasing the dose up to 60 mg daily depending on response and tolerability.

Formulation

The recommendation to offer a modified-release formulation is in line with the formulations used in nifedipine studies.

Once-daily formulations of nifedipine are preferred, as there is little difference in cost compared with twice-daily formulations and once-daily regimens are likely to be more convenient.

Immediate-release formulations are less preferred, as they may cause an exaggerated decrease in blood pressure and reflex tachycardia [ABPI Medicines Compendium, 2012b; ABPI Medicines Compendium, 2012c].

Monitoring blood pressure

CKS recommends monitoring blood pressure because of the antihypertensive and vasodilatory effects of nifedipine. This is in line with recommendations issued by the manufacturers of nifedipine.

Treatments not recommended

Which treatments are not recommended for chilblains?

The following products are not recommended for the treatment and prevention of chilblains:

Over-the-counter topical preparations marketed for the treatment of chilblains (for example Balmosa®, Deep Heat®, Mentholatum Vapour Rub®).

Capsaicin - topical (0.025% and 0.075% cream — both are only available on prescription).

Corticosteroids - oral and/or topical .

Diltiazem and other calcium-channel blockers .

Ginkgo biloba .

Vasodilators: nicotinic acid and pentoxifylline.

Alpha-blockers: phenoxybenzamine and thymoxamine.

Ultraviolet phototherapy .

Vitamin D3 .

Basis for recommendation

Basis for recommendation

Treatments other than nifedipine are not recommended for chilblains because CKS found insufficient evidence to justify their use. For further information, see Supporting evidence.

All the studies identified for the treatments listed had major methodological weaknesses. The studies were small (generally involving 10–30 participants), unblinded, and lacked a placebo group. In addition, they did not take into account confounding factors (such as outdoor temperature, exposure to cold, and outdoor activities), as highlighted by some investigators [Souwer and Lagro-Janssen, 2009].

This is supported by a literature review which also failed to find good evidence supporting any treatment for chilblains [Souwer and Lagro-Janssen, 2004].

The list of treatments not recommended is not exhaustive. There are other treatments regarded as unproven including other topical vasodilators (such as nitroglycerin creams), antihistamines, calcium preparations, intramuscular vitamin preparations, heparin ointment, and sympathectomy [Almahameed and Pinto, 2008]. CKS found no studies on these treatments.

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Nifedipine

Nifedipine

Do not prescribe nifedipine for:

People with cardiogenic shock, clinically significant aortic stenosis, or unstable angina, or during or within 1 month of myocardial infarction.

Women who are pregnant or breastfeeding — seek specialist advice if these women require treatment.

People taking rifampicin — effective plasma levels of nifedipine may not be achieved owing to enzyme induction.

Prescribe nifedipine with caution for people with the following conditions:

Hypotension — this will be aggravated, as nifedipine is an antihypertensive drug.

Poor cardiac reserve — exacerbation of heart failure has occasionally been observed with nifedipine.

Hepatic impairment — nifedipine is metabolized primarily by the liver. Some manufacturers of once-daily or twice-daily formulations state that these preparations are contraindicated in people with hepatic impairment.

Adverse effects

Most of the adverse effects of nifedipine are related to its vasodilatory effects.

Common adverse effects are headache, flushing, and oedema (that is not responsive to diuretics).

Tachycardia and palpitations may occur in the early stages of treatment.

Cardiac ischaemic pain has been reported, in a small proportion of people, after taking nifedipine.

Discontinue treatment if this occurs.

Drug interactions

Nifedipine is metabolized by cytochrome P450 isoenzymes. Consequently, the plasma level of nifedipine is:

Increased by drugs which inhibit these enzymes — for example macrolide antibiotics (such as erythromycin), protease inhibitors (such as ritonavir), azole antifungals (for example ketoconazole), cimetidine, and diltiazem.

Decreased by drugs which induce these enzymes — for example rifampicin, phenytoin, carbamazepine, and phenobarbital.

The metabolism of nifedipine is inhibited by grapefruit and grapefruit juice.

Consequently, it is recommended that people taking nifedipine avoid grapefruit and grapefruit juice.

[ABPI Medicines Compendium, 2009; ABPI Medicines Compendium, 2012a; ABPI Medicines Compendium, 2012d]

Evidence

Evidence

Supporting evidence

CKS has reviewed the evidence on a wide range of interventions available for chilblains including:

Nifedipine .

Over-the-counter topical preparations marketed for the treatment of chilblains.

Capsaicin - topical .

Corticosteroids - oral and/or topical .

Diltiazem and other calcium-channel blockers .

Ginkgo biloba .

Vasodilators: nicotinic acid and pentoxifylline.

Alpha-blockers: phenoxybenzamine and thymoxamine.

Ultraviolet phototherapy .

Vitamin D3 .

No studies were identified for the following interventions:

Other topical vasodilators — such as nitroglycerin creams.

Antihistamines.

Calcium preparations.

Intramuscular vitamin preparations.

Heparin ointment.

Sympathectomy.

Nifedipine

Evidence on nifedipine for treatment and prevention of chilblains

There is poor evidence to support the use of nifedipine for the treatment and prevention of chilblains.

The effects of nifedipine on chilblains were examined by a group of UK investigators over three winter periods [Dowd et al, 1986; Rustin et al, 1989].

The results should be viewed with caution because:

All three studies (published in two articles) involved only 10–36 participants.

The first two studies involved people with severe chronic chilblains (defined as lasting for a minimum of 5 months per year for the past 3 years), and the findings are not applicable to people with acute chilblains. No information was given in the third study on whether acute or chronic chilblains were studied.

The studies did not account for confounding factors which might influence treatment response (for example: outdoor temperature; individual factors, such as exposure to cold; and outdoor activity).

In a pilot study (1984–1985), seven of 10 women with severe idiopathic chilblains reported lesion resolution within 14 days of treatment (after titration from nifedipine 5 mg daily to the effective or maximal tolerated dose). The most commonly used dose was 60 mg daily.

On the basis of this result, a double-blind, randomized crossover trial was undertaken (1985–1986) in which 10 adults with severe idiopathic chilblains were randomized to receive modified-release nifedipine (60 mg daily) or placebo for 6 weeks, before crossing over to the alternate treatment for a further 6 weeks.

When treated with nifedipine, no new episode of chilblains was reported. Established lesions in seven participants resolved within 7–10 days of treatment.

When receiving placebo, lesions resolved more slowly (over 20–28 days), with new lesions continuing to develop. Five people initially treated with nifedipine relapsed within 1 week of starting placebo.

Pain and irritation were reported to resolve faster with nifedipine (4–5 days) than with placebo (23–25 days).

Headache, ankle swelling, and mild flushing were reported with nifedipine, with one person requiring a dose reduction (to 40 mg daily) owing to symptomatic hypotension.

The third study (1986–1987) was open-label (34 participants, age range 17–76 years) and included people with acrocyanosis, Raynaud's phenomenon, and anorexia nervosa. Modified-release nifedipine was titrated from 20 mg daily to 60 mg daily (or the maximal tolerated dose) for 2 months.

Mean clearance times for chilblain lesions varied from 8 days for hand lesions (range 7–10 days, three people taking 60 mg) to 23 days for foot lesions (range 6–42 days, 10 of 12 people were taking 40 mg or less).

Although the authors attributed the slower response to the lower dose of nifedipine used (less than 60 mg daily), this result should be interpreted with caution, given the small number of people in each group (3–14 participants) and the lack of a placebo group.

Tolerability to high-dose nifedipine was poor, with 52% of people only taking a dose of 10–40 mg daily.

Headache and facial flushing were reported with nifedipine (incidence not reported).

The efficacy of nifedipine (immediate-release 10 mg twice daily, titrated to modified-release 20 mg twice daily) was compared with diltiazem (60 mg three times a day) in a small study undertaken in Northern and Central India over three winter seasons [Patra et al, 2003].

In the diltiazem group (12 participants), only two people reported complete relief within 7 days, whereas complete relief took 21 days for three people. In contrast, the study reported that 80–90% of the nifedipine group (25 participants) responded (in an unspecified manner) by around day 14. Treatment was then continued until complete relief was obtained, ranging from 3 days for pruritus to 19–26 days for severe oedema and ulceration.

The effect of treatment cannot be assessed, given that:

The study lacked a placebo group and involved very few participants.

The findings might be influenced by marked seasonal and geographical variations, as the data were pooled from three winter seasons and from a wide geographical region.

Over-the-counter topical preparations

Evidence on over-the-counter topical preparations for treatment of chilblains

Evidence is lacking for over-the-counter topical preparations marketed for the treatment of chilblains.

Several topical preparations available over-the-counter are marketed for the treatment of chilblains (for example Balmosa®, Deep Heat®, Mentholatum Vapour Rub®). They contain ingredients (such as menthol, camphor, methyl salicylate, capsicum, methyl nicotinate, benzyl alcohol, and eucalyptus oil) which produce a localized vasodilatory, warming, or rubefacient effect.

Despite the widespread availability of these agents, CKS found no studies investigating their use for the treatment of chilblains.

Capsaicin - topical

Evidence on topical capsaicin for treatment of chilblains

There is no good evidence to support the use of topical capsaicin for the treatment of chilblains.

CKS identified one study which reported improvement in symptoms and lesions after use of topical capsaicin (0.025% cream applied three times a day for at least 10 days) [Cappugi et al, 1995]. However, the benefits of treatment could not be assessed, as the study was unblinded and non-randomized, lacked a placebo control, and involved only 10 people with chilblains.

Capsaicin 0.025% (Zacin®) and 0.075% (Axsain®) creams are available on prescription and are not licensed for the treatment of chilblains.

Corticosteroids

Evidence on corticosteroids for treatment of chilblains

There is no good evidence to support the use of corticosteroids (oral or topical) for the treatment of chilblains.

The use of corticosteroids for chilblains is controversial [Simon et al, 2005]. Some experts advocate the use of topical corticosteroids [Ganor, 1983], whereas others consider them ineffective [Almahameed and Pinto, 2008].

Topical corticosteroids are not licensed for the treatment of chilblains.

CKS identified only one published letter, favouring the use of fluocinolone acetonide 0.025% cream under an occlusive dressing in a small study involving 20 people with chilblains [Ganor, 1973].

Evidence from randomized controlled trials is lacking.

One very small, unblinded trial with 40 participants found a combination of topical and systemic corticosteroids to be less effective than pentoxifylline alone (see Pentoxifylline).

Adverse effects of topical corticosteroids have been highlighted in a case report [Burry, 1987]. Betamethasone 0.05% cream was found to cause lichenoid papules in a young woman with chilblains (with no improvement of the chilblains).

Consequently, given the lack of evidence, CKS does not recommend the use of topical or oral corticosteroids for the treatment of chilblains.

Diltiazem and other calcium-channel blockers

Evidence on diltiazem and other calcium-channel blockers for treatment of chilblains

There is no good evidence to support the use of diltiazem for the treatment of chilblains. Apart from nifedipine, CKS found no evidence on the use of other calcium-channel blockers (such as amlodipine) for the treatment of chilblains.

Only one small study was identified which compared diltiazem with nifedipine (see Nifedipine) [Patra et al, 2003].

The benefit of diltiazem could not be assessed because the study lacked a placebo control and only 12 participants (severity of chilblains unclear) were recruited in the diltiazem group. In addition, the findings might be influenced by marked seasonal and geographical variations, as the data were pooled from three winter seasons and from a wide geographical region.

CKS found no published expert reviews supporting the use of diltiazem for chilblains.

Ginkgo biloba

Evidence on ginkgo biloba for treatment of chilblains

CKS found no evidence or published expert review about the use of ginkgo biloba (based on its vasodilatory effects) for the treatment of chilblains.

Nicotinic acid

Evidence on nicotinic acid for treatment of chilblains

There is no evidence from randomized controlled trials (RCTs) to support the use of nicotinic acid (a vasodilator) for the treatment of chilblains.

CKS identified one UK trial (published in 1948) which reported nicotinic acid to be effective in resolving or relieving chilblains in 26 out of 27 unselected patients with chilblains (enrolled consecutively in general practice) [Gourlay, 1948].

Dosages used for adults and children were titrated from 50 mg and 25 mg three times daily respectively, up to 300 mg daily.

In two patients with a recurrent episode of chilblains who previously responded to nicotinic acid, substitution to nicotinamide (unknown to patients) failed to produce any improvement. The chilblains improved when nicotinic acid treatment was restarted.

Apart from this review, no other studies were identified.

Nicotinic acid (Niaspan®) is not licensed for the treatment of chilblains.

Pentoxifylline

Evidence on pentoxifylline for treatment of chilblains

There is no good evidence to support the use of pentoxifylline (a vasodilator) for the treatment of chilblains.

CKS identified only one small, unblinded trial with 40 participants (undertaken in a hospital in Baghdad, Iraq) which compared oral pentoxifylline (1200 mg daily) with a combination of oral prednisolone (0.5 mg/kg daily) and topical clobetasol ointment (strength unspecified) [Noaimi and Fadheel, 2008]. Treatment was for 2 weeks.

Although the study reported that more people in the pentoxifylline group responded to treatment (five people) than in the steroid group (three people), it was not possible to assess the benefit of treatment, given that:

Only 10–11 participants in each group completed treatment (drop-out rates of around 50%).

The study lacked a placebo group and no information was given as to if the groups were matched.

Adverse effects were not reported.

Phenoxybenzamine

Evidence on phenoxybenzamine for treatment of chilblains

There is no good evidence to support the use of phenoxybenzamine (an alpha-blocker) for the treatment of chilblains.

CKS identified one small Scottish study of double-blind design (128 participants recruited, randomization unclear) which compared phenoxybenzamine (10 mg daily, increasing up to 40 mg daily) with placebo over 4 weeks [Anderson et al, 1957].

Although more people reported complete remission with phenoxybenzamine (24 of 28) than with placebo (17 of 34), this result should be interpreted with caution, given that:

Only 62 participants completed the study, and no data on disease severity were given.

The two groups were not matched in terms of the period of treatment and observation — for example more people in the placebo group initiated therapy in December (study period December to March).

More people reported adverse effects with phenoxybenzamine, with nine people withdrawing because of adverse effects (there were no withdrawals with placebo).

Thymoxamine

Evidence on thymoxamine for treatment of chilblains

Weak evidence from one small crossover study suggests that thymoxamine (an alpha-blocker) is no more effective than placebo in treating severe chilblains.

CKS identified one small double-blind crossover trial which compared thymoxamine (160 mg daily for 2 weeks) with placebo in 33 adults with severe chilblains (cracked or ulcerated skin) [Jaffe and Grimshaw, 1980].

No difference was found between the two groups in terms of:

The number of people who reported complete resolution of their symptoms after 1 week of treatment.

Participant outcomes when the treatments were crossed over.

Ultraviolet phototherapy

Evidence on ultraviolet phototherapy for prevention of chilblains

CKS identified one very small trial which found ultraviolet phototherapy to be ineffective for the prophylaxis of chilblains.

In this UK double-blind trial, the hands or feet of nine women with chilblains were randomized to receive ultraviolet (UV) light and placebo treatment (the same lamp with a filter that absorbed the UV radiation) [Langtry and Diffey, 1989]. Treatment was given three times a week for 2 weeks (gradually increasing from 3 minutes to 20–30 minutes of exposure). Assessment was done 4 weeks after treatment and monthly for the next 2 months.

Response was variable. Three women developed chilblains, three women remained symptom free, and chilblains became worse in three women. No difference was found between the UV-treated and placebo-treated limbs.

Vitamin D3

Evidence on vitamin D3 for treatment of chilblains

Weak evidence from one small crossover study suggests that vitamin D3 2000 IU daily is no more effective than placebo in treating chronic chilblains.

In this study, 37 participants were randomized into two groups: one group received vitamin D3 for 7 weeks, and the other group received placebo for 3 weeks before changing to vitamin D3 for 4 weeks [Souwer and Lagro-Janssen, 2009]. The participants and investigators were blinded to treatment.

After correcting for confounding factors (including outdoor temperature), no differences were found between the placebo and vitamin D3 groups in terms of people reporting pain/itch or restriction to their everyday life.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of chilblains.

Search dates

July 2009 - July 2013

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Chilblains/, chilblain$.tw, pernio.tw, perniosis.tw

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSH subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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